High Calcium Crystalloid Therapy for Cardiac Arrest

(SPEAR Trial)

Overseen By Cara Spivy, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Carol Bernier

Must not be taking: Digitalis

Disqualifiers: Under 18, Pregnancy, DNR, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 hour

342 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special fluid with high calcium and low sodium, known as High Calcium, Low Sodium (HCLS) Crystalloid Therapy, can improve survival in cases of Pulseless Electrical Activity (PEA), a specific type of cardiac arrest. Typically, a salt solution is used in emergencies, but the study seeks to discover if the calcium-rich fluid enhances survival chances. Participants will randomly receive either the usual salt solution or the new high-calcium fluid during emergency care. Suitable candidates for this trial are individuals who experience PEA—a condition where the heart shows electrical activity but does not pump blood—and receive treatment from specific emergency services in Roanoke, Botetourt County, or Salem. As a Phase 2, Phase 3 trial, this research evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially life-saving advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that High Calcium, Low Sodium (HCLS) therapy might offer a new way to treat cardiac arrest, especially in cases of Pulseless Electrical Activity (PEA), where the heart has electrical activity but no pulse. Studies suggest that fluids with more calcium and less sodium might help the heart start beating again when it can't on its own.

HCLS fluid consists of FDA-approved ingredients, indicating general safety. Related studies have linked the use of calcium during cardiac arrest to positive patient outcomes. Although not the standard treatment, emergency medical services (EMS) sometimes use it for PEA cases, suggesting it is usually well-tolerated.

Overall, while researchers continue to study HCLS therapy, current research suggests it could be safe and might help improve survival rates in PEA cases. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about High-Calcium Crystalloid Therapy for cardiac arrest because it introduces a unique balance of electrolytes that could enhance resuscitation outcomes. Unlike traditional treatments that typically use standard saline solutions, this therapy uses a high-calcium, low-sodium crystalloid solution, which may improve cardiac function during emergencies. The addition of calcium chloride is thought to support the heart's ability to contract more effectively, potentially leading to better survival rates. By exploring these new electrolyte combinations, scientists hope to find more effective ways to manage cardiac arrest and improve patient recovery.

What evidence suggests that High Calcium, Low Sodium Crystalloid Therapy might be an effective treatment for Pulseless Electrical Activity?

Research has shown that a High Calcium, Low Sodium (HCLS) fluid might help patients survive Pulseless Electrical Activity (PEA), a severe type of cardiac arrest. In this trial, participants in the HCLS group will receive this specific fluid. Studies suggest that fluids with less sodium and more calcium can help activate heart cells to restart the heart. The HCLS solution consists of FDA-approved ingredients and is sometimes used by emergency medical teams for PEA. Although not the standard treatment, HCLS might improve survival rates or be as effective as usual treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Carol Bernier, DO

Principal Investigator

Virginia Polytechnic Institute and State University

Are You a Good Fit for This Trial?

The SPEAR study is for patients who experience a type of cardiac arrest called PEA, where the heart's electrical activity is normal but it doesn't contract. Participants must be treated by certain EMS providers in Roanoke and not have a DNR order, known pregnancy, untreated cardiac arrest over 30 minutes, traumatic cardiac arrest, LVAD device or digitalis toxicity.

Inclusion Criteria

I was unconscious and had no pulse but my heart wasn't in a common irregular rhythm.

Exclusion Criteria

I may have side effects from heart medication.

I experienced a heart stoppage for over 30 minutes without treatment.

I have a DNR order and do not wish to be enrolled in the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Immediate

Treatment

Patients receive either routine fluid therapy (normal saline) or a High Calcium, Low Sodium (HCLS) solution during pre-hospital care

Up to 1 hour

Follow-up

Participants are monitored for neurological outcomes and survival to hospital discharge

Up to 30 days

What Are the Treatments Tested in This Trial?

Interventions

• High Calcium, Low Sodium (HCLS) Crystalloid Therapy

Trial Overview This trial tests if High Calcium, Low Sodium (HCLS) fluid improves survival in PEA compared to standard salt solution therapy. It's a double-blind study meaning neither the patient nor provider knows which treatment is given. Patients are randomly assigned to receive either HCLS or routine fluid therapy.

How Is the Trial Designed?

Group I: High-Calcium, Low- Sodium (HCLS) group Experimental Treatment 1 Intervention

Patients will receive a drip of blinded, intravenous, half-normal saline and an unblinded, intravenous, one gram bolus of calcium chloride.

Group II: High-Calcium, High- Sodium (HCHS) group Active Control 1 Intervention

Patients will receive a drip of blinded, intravenous, normal saline and an unblinded, intravenous, one gram bolus of calcium chloride.

High Calcium, Low Sodium (HCLS) Crystalloid Therapy is already approved in United States for the following indications:

Approved in United States as High Calcium, Low Sodium Crystalloid Therapy for:

• Pulseless Electrical Activity (PEA) in cardiac arrest

Who Is Running the Clinical Trial?

Carol Bernier

Lead Sponsor

Trials

1

Recruited

340+

Virginia Polytechnic Institute and State University

Collaborator

Trials

162

Recruited

26,900+

Published Research Related to This Trial

A review of 48 studies found that administering calcium during cardiopulmonary resuscitation (CPR) does not improve survival rates from cardiac arrest, regardless of the heart's rhythm.

The role of calcium in specific conditions like hyperkalemia or calcium channel blocker intoxication remains uncertain due to limited evidence, highlighting a significant gap in research on this topic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium administration during cardiac arrest: a systematic review. Kette, F., Ghuman, J., Parr, M.[2018]

Calcium chloride has been historically used for resuscitating patients in asystole and electromechanical dissociation (EMD), but recent studies, including a randomized controlled trial, show no significant improvement in resuscitation rates or long-term survival compared to saline.

While calcium chloride may improve resuscitation rates in some EMD cases, the overall survival to hospital discharge remains very low, indicating that its routine use in asystole and EMD lacks sufficient evidence to support its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium: limited indications, some danger. Thompson, BM., Steuven, HS., Tonsfeldt, DJ., et al.[2013]

The European Resuscitation Council and American Heart Association recommend a rapid administration of calcium chloride to protect the heart during hyperkalemia, but the formulations of calcium chloride can differ across European countries.

To reduce the risk of errors in treatment, the guidelines should specify calcium doses clearly in terms of mmol/L, mEq, or mg of calcium ions, ensuring consistency in administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The amount of calcium in calcium chloride - Is there a need to clarify emergency treatment of hyperkalaemia algorithm? Putowski, M., Jaskuła, J., Woroń, J.[2023]

In a study of 104 patients with out-of-hospital cardiac arrest and pulseless electrical activity (PEA), those who received calcium chloride had a lower rate of return of spontaneous circulation (20%) compared to those who received a placebo (39%), suggesting that calcium may not be beneficial in this context.

At 30 days post-arrest, only 2.2% of patients in the calcium group were alive compared to 13.6% in the placebo group, indicating potential harm from calcium administration rather than a therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of calcium in patients with pulseless electrical activity and electrocardiographic characteristics potentially associated with hyperkalemia and ischemia-sub-study of the Calcium for Out-of-hospital Cardiac Arrest (COCA) trial. Vallentin, MF., Povlsen, AL., Granfeldt, A., et al.[2023]

In a study involving 57 dogs undergoing cardiopulmonary bypass and one hour of global myocardial ischemia, an intracellular-like calcium-bearing solution (ICS) significantly improved heart function after ischemia compared to a calcium-free extracellular-like solution (ECS) and control solutions.

The ICS showed better postischemic ventricular performance regardless of how it was administered, indicating its potential as a more effective treatment for heart function recovery after ischemic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An intracellular-like cardioplegic solution. Its enhancement of myocardial protection. Christlieb, IY., Clark, RE.[2019]

Low-calcium hemodialysis (LCHD) effectively reduced serum calcium levels in patients with hypercalcemic crisis, with an average decline of 4.63 mg/dL observed in a study of 42 patients, most of whom had malignancies.

Refractory cases, which did not respond to treatment, had significantly higher mortality rates (58.8%) compared to improved cases (10.5%), highlighting the urgency of prompt management in hypercalcemic crises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Low-Calcium Hemodialysis in the Treatment of Hypercalcemic Crisis. Trabulus, S., Oruc, M., Ozgun, E., et al.[2019]

In a study involving laboratory rats, verapamil hydrochloride was found to effectively reverse calcium-induced cardiac arrest, resulting in an impressive 83% survival rate compared to 0% in control groups.

Magnesium chloride did not demonstrate any efficacy in reversing cardiac arrest caused by high calcium levels, highlighting the potential of verapamil as a therapeutic option for hypercalcemic cardiac toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Verapamil reverses calcium cardiotoxicity. Zaloga, GP., Malcolm, D., Holaday, J., et al.[2019]

In the COCA trial involving 391 patients with out-of-hospital cardiac arrest, calcium administration after adrenaline did not improve survival rates compared to placebo, with only 4.7% of patients in the calcium group alive at 1 year versus 9.1% in the placebo group.

The study also found that fewer patients in the calcium group had a favorable neurological outcome (3.6%) compared to the placebo group (8.6%), indicating that calcium may be harmful rather than beneficial in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest. Vallentin, MF., Granfeldt, A., Meilandt, C., et al.[2022]

In a study of 111 patients with severe hyperkalemia, intravenous calcium gluconate was found to significantly improve main rhythm disorders on ECG, indicating its potential effectiveness in treating critical heart rhythm issues caused by high potassium levels.

However, the treatment did not show significant effects on non-rhythm ECG disorders, suggesting that calcium gluconate may be specifically beneficial for certain types of cardiac complications associated with hyperkalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of calcium gluconate in the treatment of hyperkalemia. Celebi Yamanoglu, NG., Yamanoglu, A.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-and-3-cardiac-arrest-1-2022-025a3?condition=cardiac+arrest&phaseList=Phase+3&overallStatus=Recruiting&hasNoPlacebo=false

High Calcium Crystalloid Therapy for Cardiac Arrest This study is trying to determine if the administration of a High Calcium, Low Sodium (HCLS) fluid in pre-hospital care will improve the chances of survival.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2364628/

Effects of resuscitation with crystalloid fluids on cardiac ... We recently demonstrated that administration of sodium bicarbonate improved the performance of the myocardium and normalized the hemodynamic parameters in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10481512/

Comparison of balanced and unbalanced crystalloids as ... In patients with cardiogenic shock, use of balanced crystalloids was associated with a similar all-cause mortality at 30 days but a lower rate ...

4. mdpi.com mdpi.com/2077-0383/12/15/5040

Saline versus Plasma Solution-A in Initial Resuscitation of ... Conclusion: Use of PS for resuscitation resulted in a faster improvement in BE and bicarbonate, especially in the early phase of post-cardiac arrest care, and ...

5. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-016-1217-5

Crystalloid fluid therapy - Critical Care - BioMed Central Early evidence suggested that sodium acetate solution was effective in restoring blood pH and plasma bicarbonate in patients suffering from ...

6. carilionclinic.org carilionclinic.org/health-and-wellness/article/study-spotlight-surviving-pea-roanoke-spear

Study Spotlight: Surviving PEA in Roanoke (SPEAR) PEA survival rates are less than 10% with traditional treatment. A new approach, HCLS (high-calcium, low-sodium) fluid, may improve outcomes for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9069921/

Association between calcium administration and outcomes ... This study aims to investigate whether calcium therapy administered during cardiac arrest at the Emergency Department is associated with good outcomes.

8. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-8-50

Effects of resuscitation with crystalloid fluids on cardiac ... We recently demonstrated that administration of sodium bicarbonate improved the performance of the myocardium and normalized the hemodynamic ...